d a n i s h m E d i c a l J O U R NAL 1
Dan Med J 61/6 June 2014
Predictive validity of neurotic disorders:
a 50-year follow-up study
Peter Winning Jepsen1, Birgitte Butler2, Stig Rasmussen3, Knud Juel4 & Per Bech2
ABSTRACT
INTRODUCTION: In 1965, Erling Jacobsen (1919-1988) de-
fended his doctoral thesis on neurosis in which he tested
the psychoanalytic theory of eridophobia as an internalising
hostility factor with a specific causality for anxiety neurosis.
He found no marked difference between anxiety neurosis
and obsessive-compulsive neurosis, which, however, both
differed from hysterical neurosis. The aim of this follow-up
study was to evaluate to which extent anxiety neurosis and
obsessive-compulsive neurosis when compared with hysterical neurosis co-existed with depression, both at the level of
diagnostic behaviour, including committed suicide, and with
regard to symptom profile.
MATERIAL AND METHODS: A total of 112 patients were followed on the Danish Central Psychiatric Research Register
and the Danish Cause of Death Register with regard to their
diagnostic behaviour. In a subset of the sample (n = 24), the
patients were assessed using the Hopkins Symptom Checklist (SCL)-90.
RESULTS: Both at the diagnostic level, including suicide rate,
and at the level of symptom severity (SCL-90), anxiety neur­
osis and obsessive-compulsive neurosis were similar, in contrast to hysterical neurosis which had no more association
with the other two categories of neurosis than would be expected by chance.
CONCLUSION: Anxiety neurosis and obsessive-compulsive
neurosis are more severe disorders than hysterical neurosis,
both in terms of symptom profile and depression, including
suicidal behaviour. The identified suicides were committed
within the first two decades after discharge from the index
hospitalisation.
FUNDING: Poul M. Færgemann’s Grant and the Neurosis
Grant of 22 July 1959.
TRIAL REGISTRATION: not relevant.
In 1965, Erling Jacobsen (1919-1988) defended his doctoral thesis on neurosis at the University of Copenhagen
in Denmark [1]. He was testing the hypothesis that in
contrast to the other categories of neurosis (obsessivecompulsive and hysterical), patients with anxiety neur­osis suffer from eridophobia, i.e. marked fear or anxiety
about situations in which feelings of aggression or hostility are triggered, or avoidance of such situations. However, he was unable to confirm this hypothesis [1]. Antiaggressive behaviour was seen in both anxiety neurosis
and obsessive-compulsive neurosis [2].
With the advent of the Diagnostic and Statistical
Manual of Mental Disorders (DSM)-III in 1980 [3], the
term neurosis was eliminated because it was found that
neurosis was mainly used for non-psychotic disorders,
i.e. as an exclusion criterion for the presence of psych­
otic disorder. In the beginning of the 1980s, Jacobsen
asked us to perform a follow-up on his original sample of
patients in order to investigate the stability of the diagnoses and establish their predictive validity regarding
morbidity and mortality [4]. We have previously published a description (in Danish) of our 50-year follow-up
results based on data from the Danish registers [5].
However, the register-based data do not contain information regarding psychopathological symptoms. Thus,
in the present analysis, we aimed at investigating the
long-term predictive validity of the three neurosis diagnoses assigned by Jacobsen, using both longitudinal
regis­ter data regarding suicide/diagnostic conversion,
and recent self-ratings on the Hopkins Symptom
Checklist (SCL)-90 [6]. Specifically, we aimed at answering the following research questions:
1. Is the concordance between the original categories
of neurosis and the equivalent DSM-III categories
adequate?
2. Will some patients initially diagnosed with a neurotic
disorder develop depression as a coexistent state?
3. Will some patients initially diagnosed with a
neurotic disorder develop a co-morbid disorder
such as schizophrenia or dementia (i.e. multiple
diagnoses)?
4. Does the suicide rate observed over the follow-up
period differ between the three types of neurotic
disorders (anxiety, obsessive-compulsive, hyster­
ical) and from the suicide rate in the background
population?
5. Does the total score on the SCL-90 and the Anxiety/
neurosis subscale of the SCL-90 (SCL-ASS) differ
from those of the background population at the
50-year follow-up?
MATERIAL AND METHODS
The original sample of patients included in the study by
Jacobsen [1, 5] consisted of 30 males and 82 females
who had been inpatients at a hospital for neurotic dis­
Original
article
1) Psychiatric Central
Referral Unit, Region of
the Capital, Mental
Health Services
2) Psychiatric Research
Unit, Psychiatric Centre
North Zealand, Hillerød
3) Psychiatric Practice,
Hillerød
4) National Institute of
Public Health,
University of Southern
Denmark, Copenhagen
Dan Med J
2014;61(6):A4858
  2 d a n i s h m E d i c a l J O U R NAL
Dan Med J 61/6 June 2014
orders between 1952 and 1955. In total, 44 patients
were classified as having anxiety neurosis, 34 patients as
having obsessive-compulsive neurosis and 34 patients as
having hysterical neurosis [1]. All patients were diagnosed in accordance with the Danish Psychiatric Associ­
ation’s Diagnostic System for Mental Disorders from
1952 [7].
In order to obtain permission to conduct the SCL-90
follow-up, we contacted the relevant Regional Ethical
Committee (Zealand and Bornholm). The Ethical Committees considered our proposed follow-up a “pilot
study”, and allowed us to contact the patients by letter
if we obtained approval to do so from their family doctors. Thus, only upon the family doctors’ acceptance did
we proceed to contact the patients by letter. In the
spring of 1992, Birgitte Butler contacted and subsequently visited 24 patients who all completed the SCL90. In the present analysis, we focused on the total score
of the SCL-90 as an overall measure of psychopathology
at follow-up, and on the eight-item SCL-ASS which
covers symptoms of nervousness, worrying, suddenly
being scared for no reason, spells of panic, obsessive
thoughts, repeated behaviour, simple phobia and social
phobia [8]. In a recent study based on a large sample of
day-patients from a Danish psychiatric hospital, we demonstrated that the SCL-ASS is a psychometrically valid
measure for the severity of anxiety/neurosis [9].
Below, the methodology for each specific research
question is explained in further detail:
ish Psychiatric Central Register during the last five years
of our follow-up period from 1994 to 2000. In the ICD-8
classification, depressive episodes were categorised as
being either endogenous (296.29) or non-endogenous
(298.09). We focussed on the coexistence of the patients
with more severe degrees of depression, using the term
coexistence as proposed by Guze [14] when two clinical
syndromes are present within the same illness. Thus, coexistence is interpreted according to Guze [14] as homo­
genous syndromes in the sense that they refer to a single
disorder with a coherent aetiology.
Research question 1: concordance between the 1952
diagnoses of neurosis and DSM-III
We had access to the patient records and were able to
translate the original neurosis diagnoses into DSM-III
diagnoses using the modified Multi-axial Classification of
Depression (MUTICLAD) system [10]. In order to compare the concordance between the original diagnoses of
anxiety neurosis, obsessive-compulsive neurosis and
hysterical neurosis with the corresponding DSM-III diagnoses (panic disorder/generalised anxiety disorder
(GAD), obsessive compulsive disorder (OCD) and conversion disorder respectively), we used Cramér’s V coefficient [11].
Research questions 5: predictive syndromatic validity
The SCL-90 total score and the SCL-ASS score of the
neur­osis patients were compared against corresponding
values for the Danish general population [16].
Research question 2: coexistence with depression
In this part of the study regarding change to other cat­
egories, we used data from the Danish Psychiatric Central
Register [12, 13]; we followed the patients until 31 December, 2000 [5]. Until 1994, the Danish Psychiatric Central Register used the International Classification of Diseases (ICD)-8 diagnostic system (WHO 1967). In 1994, the
ICD-10 diagnostic system (WHO 1993) was implemented,
but all our patients have been classified in accordance
with ICD-8 as none of our patients appeared in the Dan-
Research question 3: co-morbidity with schizophrenia
or dementia
To evaluate co-morbidity between the neurotic disorders and the ICD-8 categories of 295 (schizophrenia) and
290-294 (organic mental disorders), we again used data
from the Danish Psychiatric Central Register. The term
co-morbidity is used in accordance with Guze [14] when
referring to two or more quite different illnesses.
Research question 4: prediction of suicide
Concerning death by suicide, we followed the patients
until 31 December 2004 [5] by means of the Danish
Regis­ter of Causes of Death [15]. Potential excess mortality due to suicide among the neurosis patients was examined by calculating the ratio between the observed
number of suicides and the expected number (standardised mortality ratio (SMR)).
Ethics
The study was approved by the Danish Civil Registration
System, the Danish Psychiatric Central Research Register
and the Danish Data Protection Agency.
Trial registration: not relevant.
RESULTS
The patients were born between 1918 and 1938. Their
median age was 31 when they were treated at the hospital for neurotic patients between 1952 and 1957 [5].
Concerning research question 1, Table 1 shows the
association between the original categories of neurosis
according to the Danish Psychiatric Association’s diagnostic system and the corresponding DSM-III diagnoses.
The Cramér V coefficient was 0.74 (p < 0.01), indicating an acceptable concordance (research question 1).
On this background, further analyses were performed
using the original categories of neurosis.
d a n i s h m E d i c a l J O U R NAL 3
Dan Med J 61/6 June 2014
Table 1 shows the concordance between the ori­
ginal categories of neurosis and the corresponding DSMIII diagnoses for the 24 patients who completed the SCL90. The Cramér V coefficient was 0.70 (p < 0.01)
Concerning research question 2, Table 2 shows the
50-year follow-up for identification of patients who
developed coexistence with depression. In total, six
members of the group of patients with anxiety neurosis
developed depression. In the two other groups, two patients in each group developed depression. Numerically,
therefore, the group of anxiety neurosis had a closer coexistence with depression.
Concerning research question 3 for identification of
patients who developed co-morbidity with schizophrenia and dementia, Table 2 shows that only patients with
obsessive-compulsive neurosis developed co-morbidity
with schizophrenia. Rather few patients developed comorbidity with dementia.
Concerning research question 4, the prediction of
suicide, Table 3 shows that for both obsessive-compulsive neurosis and anxiety neurosis, the range of SMR for
suicide was from over 1 to 18 (p < 0.05), whereas in hysterical neurosis the results ranged from 0.1 to 14.7,
which is identical to the levels encountered in the gen­
eral population. The suicides were committed during the
first two decades of the follow-up period.
Table 4 shows the results related to the final research question. Once again, the patients in the hyster­
ical neurosis group scored similarly to the general
Danish population, especially on the SCL-ASS. The hysterical neurosis group of patients only scored higher
than the general population on the somatisation subscale, but scores were lower than those of both obsessive-compulsive neurosis and anxiety neurosis. In all
comparisons (Table 4), obsessive-compulsive neurosis
scored highest, but anxiety neurosis followed closely as
reflected by the total SCL-90 scores.
DISCUSSION
We found an acceptable concordance between Jacob­
sen’s original diagnosis of the three categories of neur­
osis and the corresponding DSM-III diagnoses (the first
research question), which justifies that focus was solely
on the original diagnoses of neurosis in this analysis of
the follow-up results. Concerning our second question, it
seemed that the coexistence between neurosis and depression was most pronounced for anxiety neurosis,
which indicates that the patients have been suffering
from the same kind of illness. However, for the fourth
research question concerning the prediction of suicide,
there was a statistically significant coexistence with both
anxiety neurosis and obsessive-compulsive neurosis. In
this context, the final research questions are of import­
ance because unlike hysterical neurosis, both obsessive-
TablE 1
The concordance between the original diagnosis of neurosis and the DSM-III categories. The values are
n (%).
The Danish Psychiatric Association,
Diagnostic System for Mental Disorders, 1952
DSM-III, 1980,
corresponding diagnoses
anxiety neurosis
obsessive-compulsive
neurosis
hysterical
neurosis
Overall (N = 112)
33 (75.0)
5 (14.7)
OCD
Panic/GAD
1 (2.3)
25 (73.5)
0 (0.0)
Conversion
0 (0.0)
0 (0.0)
19 (55.9)
Dysthymia
4 (9.1)
1 (2.9)
1 (2.9)
Other diagnoses
6 (13.6)
3 (8.8)
7 (20.6)
Total
44 (100.0)
7 (20.6)
34 (100.0)
34 (100.0)
Subgroup who completed
the SCL-90 (N = 24)
Panic/GAD
5 (62.5)
1 (14.3)
2 (22.2)
OCD
1 (12.5)
5 (71.4)
0 (0.0)
Conversion
0 (0.0)
0 (0.0)
5 (55.5)
Dysthymia
1 (12.5)
1 (14.3)
0 (0.0)
Other diagnoses
1 (12.5)
0 (0.0)
2 (22.2)
Total
8 (100)
7 (100)
9 (100)
DSM-III = Diagnostic and Statistical Manual of Mental Disorders, 3rd ed.; GAD = generalised anxiety
disorder; OCD = obsessive compulsive disorder; SCL = Hopkins Symptom Checklist.
TablE 2
The 50-year follow-up for identification of patients who developed ICD-8 categories (coexistence with
depression or co-morbidity with schizophrenia or dementia). The values are n.
The Danish Psychiatric Association,
Diagnostic System for Mental Disorders, 1952
Final ICD-8 categories
anxiety neurosis
obsessive-compulsive
neurosis
hysterical
neurosis
Coexistence with depression
Endogen (296)
Non-endogen (298)
4
2
2
0
2
0
Co-morbidity with schizophrenia (295)
Paranoides
Pseudoneurotica
Uncertain
0
0
0
1
1
1
0
0
0
Co-morbidity with dementia (291-294)
0
2
1
Total
6
7
3
ICD-8 = International Classification of Disease, 8th version.
TablE 3
The distribution of committed suicides over the 50-year follow-up.
The Danish Psychiatric Association.
Diagnostic system for mental disorders, 1952
Standardised mortally
ratios due to suicide
anxiety neurosis
(n = 44)
obsessivecompulsive
neurosis (n = 34)
hysterical neurosis
(n = 34)
Standardised
mortality ratio
(95% confidence interval)
7.2
(2.0-18.5)
6.2
(1.3-18.0)
2.6
(0.1-14.7)
  4 d a n i s h m E d i c a l J O U R NAL
Dan Med J 61/6 June 2014
TablE 4
The distribution of the
HSCL-90 subscales (N =
24) mean (± standard deviation). Compared to
[16].
The Danish Psychiatric Association’s
Diagnostic System for Mental Disorders, 1952
HSCL-90
subscales
anxiety
(n = 8)
OCD
(n = 7)
hysteria
(n = 9)
General population
normal (n = 1.153)
p-value
HAM-D16
0.91 (± 0.42)
1.48 (± 1.28)
0.80 (± 0.35)
0.68 (± 0.62)
0.02
HAM-D6
1.04 (± 0.67)
1.38 (± 1.46)
0.85 (± 0.46)
0.76 (± 0.76)
> 0.10
HAM-D9
0.81 (± 0.53)
1.59 (± 1.19)
0.79 (± 0.42)
0.66 (± 0.61)
0.01
HAM-Dsuicide
1.12 (± 1.25)
1.14 (± 1.35)
0.56 (± 0.88)
0.45 (± 0.84)
0.09
HAM-A14
HAM-A6
SCL-ASS
1.02 (± 0.50)
1.31 (± 0.92)
1.03 (± 0.63)
1.40 (± 1.11)
1.52 (± 1.23)
1.55 (± 1.22)
0.72 (± 0.24)
0.91 (± 0.34)
0.44 (± 0.28)
0.58 (± 0.55)
0.75 (± 0.66)
0.42 (± 0.47)
0.001
0.02
< 0.001
Interpersonal sensitivity
0.97 (± 0.59)
1.63 (± 1.14)
0.71 (± 0.58)
0.84 (± 0.70)
> 0.10
Somatization subscale
1.22 (± 0.70)
1.26 (± 1.04)
0.87 (± 0.54)
0.49 (± 0.53)
0.001
Total HSCL-90
0.85 (± 0.37)
1.21 (± 0.94)
0.56 (± 0.23)
0.45 (± 0.43)
0.001
HAM-A6 = Hamilton Anxiety Scale, core items; HAM-A14 = Hamilton Anxiety Scale, full scale; HAM-D6 = Hamilton Depression Scale, core items; HAM-D9 =
Hamilton Depression Scale, arousal items; HAM-D16 = Hamilton Depression Scale, full scale; HAM-Dsuicide = Hamilton Depression Scale, suicide item;
HSCL-90 = Hopkins Symptom Checklist, full scale; OCD = obsessive compulsive disorder; SCL-ASS = Hopkins Symptom Checklist anxiety subscale.
compulsive neurosis and anxiety neurosis scored higher
than the general population on the SCL-90.
Thus anxiety neurosis and obsessive-compulsive
neurosis have a common factor of severity when compared with hysterical neurosis. This conclusion is in accordance with the original works by Freud and Janet.
In his original description of the clinical symptomatology
of “Die gemischte Neurose”, Freud [17] stated that we
have to distinguish the mixed neurosis from those symptoms which belong neither to neurasthenia nor to hys­
teria.
The mixed neurosis goes from anxiety neurosis, including anxiety attacks, to phobias and obsessional
thoughts [17]. The mixed neurosis was found to have no
more association with hysteria than would be expected
by chance [18].
When Jacobsen asked us to perform a follow-up on
the patients he so intensively investigated in the 1950s,
it was his impression from his later clinical work, especially with patients he treated with antidepressants, that
The Danish psychiatrist Erling Jacobsen.
Drawing by Torben
Bendix, 1982.
anxiety neurosis coexisted with depression. He was
aware of the work by Hoch and Polatin [19] describing
how patients with neurotic symptoms might develop
schizophrenia-like symptoms, which, however, were
often different from the classic types of schizophrenia.
In our follow-up analysis, three patients developed
symptoms within the schizophrenic spectrum; all were
from the original group of obsessive-compulsive neur­
osis. These three patients were actually also classified by
the DSM-III as having obsessive-compulsive disorders.
Obsessive symptoms may occur in schizophrenia, but
are here of a rather bizarre form [20]. As discussed by
Guze [14], co-morbid illnesses such as obsessive-compulsive neurosis and schizophrenia are very important to
identify because treatment with antidepressants may
adversely affect the outcome in schizophrenia. In other
words, it is two different kinds of illnesses. On the other
hand, the coexistence of anxiety neurosis with depression refers to the same underlying illness which implies
that the therapeutic approach is quite similar.
In general, however, we found the consistency of
the original neurotic categories (anxiety, obsessive-compulsive and hysteria) to be very high over the 50 years of
follow-up. We found no superiority of the corresponding
DSM-III categories over the original neurotic categories.
In the very few cases in which obsessive-compulsive
neurosis was co-morbid with schizophrenia, the diagnostic hierarchies in the ICD-8 would force the diagnostician
to use only one category: schizophrenia. Within the neurotic disorders, we found that the anxiety and obsessivecompulsive categories have no higher association with
hysteria than would have been expected by chance in
terms of depression or suicidal behaviour. In these cases, coexistence between anxiety and depression should
be considered rather than co-morbidity.
Dan Med J 61/6 June 2014
CORRESPONDENCE: Per Bech, Voksenpsykiatrisk Afsnit, Psykiatrisk Center
Nordsjælland, Hillerød, Dyrehavevej 48, 3400 Hillerød, Denmark.
E-mail: [email protected]
ACCEPTED: 30 March 2014.
CONFLICTS OF INTEREST: Disclosure forms provided by the authors are
available with the full text of this article at www.danmedj.dk.
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